Setting CLL Treatment Goals and a Plan That’s Right for You

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Topics include: Treatments

As more oral, targeted therapies are available, can a patient’s chronic lymphocytic leukemia (CLL) genetics indicate which therapy will be most effective? Who will benefit from novel agents? CLL expert Dr. Philip Thompson, from The University of Texas MD Anderson Cancer Center, reviews the goals of CLL care based on age, fitness, treatment history and overall health. Dr. Thompson also discusses the prognostic factors that influence treatment decisions and how to determine which patient subset will tolerate a treatment best. 

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Andrew Schorr:

So, okay.  So how do you know what—and this get to the goals of treatment.  Like for instance the FCR acronym, fludarabine (Fludara), cyclophosphamide (Cytoxan) and rituximab (Rituxan) that I had years ago, some people have and Carol had.  So that was six months of infused therapy.  Now you have oral therapies.  Now you have oral therapies combined with infused therapies.  You have some traditional chemotherapy drugs, like the cyclophosphamide and all that that sort of blasts a lot of stuff, and you have other targeted therapies.  So what discussion do you have with people about what's right for you? 

But actually some of these tests will tell us you'll respond to therapy A but you won't respond to therapy B, so we're heading into a world of kind of individualized therapy based on what a patient's CLL genetics are like and also I guess based on what the patient themselves is like.   

But the two things that enable me to decide what's the best option for a patient is what are the genetics of this patient's CLL and what are the—I guess how old is a patient, how fit is a patient, what are their other medical problems because those things will enable me to determine will they tolerate the treatment well.  

So the traditional—I guess, prior to 2010 we treated most patients with two regimens.   

The younger, fitter patients would get FCR or something similar to FCR, which is a relatively intense multiagent chemotherapy or chemoimmunotherapy treatment, and that is very good at getting the CLL down, but perhaps an older patient or a patient who's got other medical problems might not be able to tolerate the FCR well. 

And then the other thing we used was chlorambucil, which is an oral chemotherapy medication which we tended to give to older patients we didn't think would be able to cope with FCR. Now we have this whole array, as you said, of oral targeted therapies, and the advantage of these oral targeted therapies—well, there are two major advantages.  One is they tend to be easier to take for patients than FCR.   

The second is they work better than FCR in certain situations, in particular patients who have a 17p deletion or a mutation in this TP53 gene, because those patients don't tend to respond well to immunotherapy.   

So I guess it then brings us to a discussion with patients about what is the goal of care.  So in a young person, maybe someone in their 60s or younger, the ideal treatment I think you want to have is something you can take for a short time and then hopefully get a very long remission from the treatment, and in that sense we're hoping for 10 years or more and potentially even for some patients a cure of the disease.  

Whereas for a patient maybe who is 80 and has a lot of other medical problems, the main goal may be you want to control the disease,

have minimal symptoms from the disease, minimal symptoms from the treatment and have a good quality of life without necessarily needing to have a 10- or 15-year remission.  So that's where the kind of patient and the genetics comes in.  

Now, in terms of the genetics, we've worked out a profile for the group of patients who are likely to have a very long?term remission from FCR.  Again, it's not perfect, it's not a crystal ball, but we've identified a group of patients where about 60 percent of them we think are potentially cured with FCR.  

So the conversation I tend to have with patients once I have all of these prognostic factors back is, this is the prognostic group you're in, this is what I would expect if I gave you FCR, and this is what I can expect from some of the newer therapies.

Now, the new therapy that's approved for untreated patients by the FDA is a drug called ibrutinib (Imbruvica), a pill that you take every day, and it blocks a protein called BTK in the CLL cells that they need to grow.  It's very effective at reducing lymph nodes, at reducing the white count, at improving other blood counts and improving symptoms, but most patients end up with a small amount of CLL left over.  And what that means is you pretty much have to take the drug indefinitely. 

And so it then gets to a conversation about, well, do you want to take a pill every day for the rest of your life.  And so some patients who have the good?risk CLL that do well with FCR may prefer to say, okay, I'm going to take six months of treatment and then I'm done for a long time rather than taking pills for the rest of their life.  

So I guess there are those two different treatment paradigms that we can offer.  

But the really important thing about the prognostic factors is that if you have, say, a 17p deletion on your CLL the average remission after FCR for a patient like that is only about a year, and generally when the disease comes back it comes back worse than what it was before.  And so for patients like that they tend to do much better with some of these new drugs like ibrutinib than they do with FCR, and that's a conversation that you can have [with your physician.]

You have venetoclax, or Venclexta, and you have others coming.   

So that's important to keep in mind when you're talking about what the first treatment is going to be. But we do like to, you know, with the first treatment, some of the clinical trials that we've been doing, we've been trying to target the treatment paradigm to specific patient populations, like I was saying, but overall what we've been trying to do is design a treatment that has the least amount of toxicity to get the deepest response that we possibly can and the longest remission, hopefully without needing indefinite therapy.  And so that's where we're moving with the clinical trials.  

But for a lot of patients that are not on a clinical trial, indefinite treatment with an oral medication is still going to be a really good option because you can get a prolong disease control that way.  

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on September 9, 2019